caArray_vince-00013: Integrated Genomics and Transcriptomic Analyses of Ductal Carcinoma In situ of the Breast

Purpose: To gain insight into genomic and trancriptomic subtypes of ductal carcinomas in situ of the breast (DCIS). Results: Thirty-two DCIS exhibited a luminal phenotype; 21were ERBB2 positive, and 4 were ERBB2/estrogen receptor (ER) negativewith1harboring a bona fide basal-like phenotype.Based on a CGHanalysis, genomic types were identified in this series of DCISwith the 1q gain/16q loss combination observed in 3 luminal DCIS, themixed amplifier pattern including all ERBB2,12 luminal and 1ERBB2/ER- DCIS, and the complex copy number alteration profile encompassing 14 luminal and 1ERBB2/ER- DCIS. Eight cases (8 of 57; 14%) presented aTP53 mutation, all being amplifiers. Unsupervised analysis of gene expression profiles of 26 of the 57 DCIS showed that luminal and ERBB2-amplified, ER-negative cases clustered separately.We further investigated the effect of high and low copy number changes on gene expression. Strikingly, amplicons but also low copy number changes especially on 1q, 8q, and 16q in DCIS regulated the expression of a subset of genes in a very similar way to that recently described in invasive ductal carcinomas. Conclusions: These combined approaches show that the molecular heterogeneity of breast ductal carcinomas exists already in in situ lesions and further indicate that DCIS and invasive ductal carcinomas share genomic alterations with a similar effect on gene expression profile. Experimental Design: We did a combined phenotypic and genomic analysis of a series of 57 DCIS integrated with gene expression profile analysis for 26 of the 57 cases. vince-00013 Assay Type: Gene Expression Provider: Affymetrix Array Designs: HG-U133A Organism: Homo sapiens (ncbitax) Tissue Sites: Breast, Breast Material Types: cDNA, genomic_DNA, total_RNA Cell Types: Ductal carcinoma in situ Disease States: Breast Carcinoma